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Updated: Oct 24, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Characterization of the mitochondrial genome in childhood multiple sclerosis. II. Multiple sclerosis without optic
E Wilichowski1, A Ohlenbusch, F Hanefeld
1Universitäts-Kinderklinik, Abteilung Pädiatrie, Schwerpunkt Neuropädiatrie, Göttingen, Germany.
Abstract:
The occurrence of mitochondrial mutations with primary pathogenic significance for Leber's hereditary optic neuropathy in patients with a multiple sclerosis-like phenotype and the preferential maternal transmission points to an involvement of the mitochondrial genome in conferring increased susceptibility to MS. To evaluate the link between MS and mtDNA variations we investigated a total of thirteen children with MS as well as twenty controls by sequencing eight mitochondrial encoded genes which are known to be the loci for LHON-associated mutations. Numerous synonymous nucleotide substitutions and common polymorphisms were excluded from comparative analyses. No primary LHON mutations were found. Secondary LHON mutations were identified more frequently in control subjects than in the children with MS. The remaining eight discrete missense mutations were chosen for further characterization. Only two of them were found in more than one patient. Our results suggest that nucleotide substitutions within the ND1, ND2, ND4, ND5, ND6, COI, COIII or cytochrome b genes of mtDNA do not contribute to the etiology of typical MS. However, the association of LHON mutations with visual impairment in MS as well as the relationship between phenotypic diversity in certain subgroups of patients with individual mtDNA genotypes merits further investigations.
Insights
Mitochondrial DNA variations, specifically Leber
Area of Science:
- Genetics and Neurology
- Mitochondrial Genomics
- Neuroimmunology
Background:
- Mitochondrial DNA (mtDNA) mutations, particularly those causing Leber's hereditary optic neuropathy (LHON), have been observed in patients with multiple sclerosis (MS)-like symptoms.
- Preferential maternal transmission of these mutations suggests a potential role for the mitochondrial genome in MS susceptibility.
- Investigating mtDNA variations is crucial for understanding the genetic underpinnings of complex neurological disorders like MS.
Purpose of the Study:
- To evaluate the association between multiple sclerosis (MS) and mitochondrial DNA (mtDNA) variations.
- To investigate the presence of Leber's hereditary optic neuropathy (LHON)-associated mutations in children with MS.
- To determine if specific mtDNA gene mutations contribute to the etiology of typical MS.
Main Methods:
- Sequencing of eight mitochondrial-encoded genes known for LHON mutations in thirteen children with MS and twenty controls.
- Exclusion of synonymous nucleotide substitutions and common polymorphisms from comparative analyses.
- Characterization of identified missense mutations, focusing on those found in more than one patient.
Main Results:
- No primary Leber's hereditary optic neuropathy (LHON) mutations were detected in the MS patient cohort.
- Secondary LHON mutations were found more frequently in control subjects than in children with MS.
- Only two out of eight discrete missense mutations were identified in more than one MS patient, suggesting limited contribution to typical MS.
Conclusions:
- Nucleotide substitutions in specific mtDNA genes (ND1, ND2, ND4, ND5, ND6, COI, COIII, cytochrome b) do not appear to be a significant etiological factor in typical multiple sclerosis (MS).
- The observed association of LHON mutations with visual impairment in MS warrants further investigation.
- The relationship between phenotypic diversity in specific MS subgroups and individual mtDNA genotypes requires additional research.
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